Inhibition of diverse opportunistic viruses by structurally optimized retrograde trafficking inhibitors

结构优化的逆行运输抑制剂抑制多种机会性病毒

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作者:Dhimant Desai, Matthew Lauver, Alexandria Ostman, Linda Cruz, Kevin Ferguson, Ge Jin, Brianne Roper, Daniel Brosius, Aron Lukacher, Shantu Amin, Nick Buchkovich

Abstract

Opportunistic viruses are a major problem for immunosuppressed individuals, particularly following organ or stem cell transplantation. Current treatments are non-existent or suffer from problems such as high toxicity or development of resistant strains. We previously published that a trafficking inhibitor that targets a host protein greatly reduces the replication of human cytomegalovirus. This inhibitor was also shown to be moderately effective against polyomaviruses, another family of opportunistic viruses. We have developed a panel of analogues for this inhibitor and have shown that these analogues maintain their high efficacy against HCMV, while substantially lowering the concentration required to inhibit polyomavirus replication. By targeting a host protein these compounds are able to inhibit the replication of two very different viruses. These observations open up the possibility of pan-viral inhibitors for immunosuppressed individuals that are effective against multiple, diverse opportunistic viruses.

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